Phase 2 study of azacitidine (AZA) and venetoclax (VEN) as maintenance therapy for acute myeloid leukemia (AML) patients in remission.
Authors: Alexandre Bazinet, Hagop M. Kantarjian, Gautam Borthakur, Musa Yilmaz, Prithviraj Bose, Elias Jabbour, Yesid Alvarado Valero, Kelly Sharon Chien, Naveen Pemmaraju, Koichi Takahashi, Nicholas James Short, Naval Guastad Daver, Ghayas C. Issa, Nitin Jain, Debra Bull-Linderman, Courtney Denton Dinardo, Guillermo Garcia-Manero, Koji Sasaki, Farhad Ravandi, Tapan M. Kadia
Journal: Journal of Clinical Oncology (2022)

e19018 Background: Most patients (pts) with AML achieve remission with current therapies but rates of relapse are high. Maintenance with oral AZA (CC-486) has been shown to prolong overall survival (OS) and relapse-free survival (RFS) in SCT-ineligible patients with AML in remission. The addition of VEN to maintenance regimens should be explored. Methods: We designed a phase 2, single-center, single-arm study to evaluate the efficacy and tolerability of AZA + VEN maintenance in AML. Pts ≥ 18 years in first remission (CR1) after induction and 1+ consolidations not immediately eligible for SCT were treated with AZA 50 mg/m2 IV/SQ on D1-5 and VEN 400 mg on D1-14 (or D1-7 at physician discretion) every 28 days, up to 24 cycles. Pts in CR2 and beyond were eligible if positive for minimal residual disease (MRD). Both intensive (INT; int/high dose cytarabine-based) and low-intensity (LOW; HMA/LDAC-based) induction regimens were permitted, including prior VEN. The primary outcome was modified RFS (mRFS; enrollment to relapse or death). Key secondary objectives were OS (enrollment to death), safety, and MRD clearance. Results: As of Feb 10 2022, 33 pts have been enrolled (characteristics in Table). The median number of cycles given is 6 (range 1-23). 20 pts (61%) received 7 days and 13 (39%) received 14 days of VEN. To date, 8 relapses and 6 deaths (all after relapse or SCT) have occurred. 5 pts (15%) have gone off protocol for SCT (censored at time of SCT). Median mRFS is not reached (NR) in both the INT and LOW cohorts (1-yr mRFS 73.9% and 58.3%, respectively). When stratified by ELN 2017, mRFS was NR, NR, and 4 mo for favorable, intermediate, and adverse risk, respectively (6-mo mRFS 92.3%, 90%, and 44.4%). Median OS is NR in both the INT and LOW cohorts (1-yr OS 93.8% and 53.3%, respectively). mRFS was numerically higher in pts with VEN exposure as part of their induction regimen (1-yr mRFS 79.1% vs 55.6% in non-VEN-exposed pts, p=0.067). Of the 7 MRD(+) pts at enrollment, 2 (29%) cleared their MRD on AZA/VEN maintenance. MRD(+) pts had a median mRFS of only 4 mo compared to NR in the MRD(-) pts (p=0.001). The MRD(+) pts in our study were very high risk (5/7 ELN adverse, 3/7 complex karyotype). The most common grade 3/4 AEs were infections (18%), thrombocytopenia (15%), neutropenia (12%), and neutropenic fever (6%). 4/33 pts (12%) required C2 VEN dose reduction for cytopenias. Conclusions: AZA/VEN maintenance is effective and tolerable in AML pts not immediately eligible for SCT after intensive or low-intensity induction. The regimen yields encouraging mRFS and OS durations. Longer follow-up and comparative studies are needed to confirm these initial results. Clinical trial information: NCT04062266. [Table: see text]